Creatine: Counteracts Cachexia and Supports Methylglyoxal

Background:

Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. It is produced in the human body from the amino acids glycine and arginine.

Creatine supplements are widely used by athletes, bodybuilders, wrestlers, sprinters, and others who wish to gain muscle mass, and recently, it has been emerged as a treatment to several diseases, including those characterized by skeletal muscle loss and dysfunction – creatine supplementation is able to increase skeletal muscle strength in fibromyalgia patients and to mitigate the decline of skeletal muscle function during aging. (Ref.)

I was shortly researching Creatine due to its supportive role in the treatment using Methylglyoxal, as it seems to strongly support that: “Amazingly, when creatine was added in combination with methylglyoxal plus ascorbic acid the tumor mass reduced to the size of contralateral normal leg muscle indicating total regression of tumor (Fig. 3).” (Ref.)

However, next to its supportive role for the Methylglyoxal treatment, Creatine seems to also have some anti tumor properties and maybe even more important for some, it has serious anti chachexia properties and as a result it was recently proposed as a nutritional supplement to counteract cancer cachexia (Ref.).

Therefore, supplementation with Creatine increases strength, power, and muscle mass and may counteract cancer cachexia while also possibly having antitumor properties and furthermore support the anti cancer effect of Methylglyoxal.

Note that Creatine supplementation may counteract the side effects of glucocorticoid administration on skeletal muscle

Mechanism:

There are several reports of the anticancer effect of creatine and cyclocreatine, and different explanations such as inhibition of glycolysis, generation of acidosis were proposed. However, in a recent report it has been suggested that tumor tissue supplemented with creatine might sequester significant amount of ATP that is necessary for any growth-oriented cells such as malignant cells. Nevertheless, the anti cancer effect of creatine is not yet clear. Various potential mechanisms have been discussed in teh following reference: http://publicationslist.org/data/theo.wallimann/ref-253/Ray-CK_Creatine_anti-cancer.AAS-2011.pdf

Extensive research has shown that oral creatine supplementation at a rate of 5 to 20 grams per day appears to be very safe and largely devoid of adverse side-effects (Ref.) I would anyway, probably take about 2-3g/day.

Safety and Toxicity:

There were no side effects reported throughout the animal or human studies (Ref.1, Ref.2) It is widely used in humans and its safety profile is very good.

Source:

Creatine is endogenously synthesized or ingested from diet (mainly meat). In addition, creatine can be ingested as a supplement, mainly in the monohydrate form.

Cancer cachexia is a complex multifactorial syndrome characterized by loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Recently, some amino acids and other amine dietary supplements have been highlighted in medical field due to positive effects upon diseases evolving skeletal muscle atrophy. Therefore, the aim of this brief review is to discuss the putative application of amines as dietary supplements to counteract skeletal muscle wasting on cancer cachexia. Specifically, we focus in two nutritional supplements: (1) branched-chain amino acids (BCAAs) and (2) creatine. Both BCAAs and creatine may attenuate proteolysis and enhance proteins synthesis in skeletal muscle. Although more experimental studies and clinical trials are still necessary to elucidate this therapeutic application, several evidences have demonstrated that amines supplementation is a promising coadjuvant treatment to cancer cachexia.

The creatine/creatine kinase (CK) system plays a key role in cellular energy buffering and transport. In vertebrates, CK has four isoforms expressed in a tissuespecific manner. In the process of creatine biosynthesis several other important metabolites are formed. The anticancer effect of creatine had been reported in the past, and recent literature has reported low creatine content in several types of malignant cells. Furthermore, creatine can protect cardiac mitochondria from the deleterious effects of some anticancer compounds. Previous work from our laboratory showed progressive decrease of phosphocreatine, creatine and CK upon transformation of skeletal muscle into sarcoma. It was convincingly demonstrated that prominent expression of creatine-synthesizing enzymes L-arginine: glycine amidinotransferase and N-guanidinoacetate methyltransferase occurs in sarcoma, Ehrlich ascites carcinoma and sarcoma 180 cells; whereas, both these enzymes are virtually undetectable in skeletal muscle. Creatine transporter also remained unaltered in malignant cells. The anticancer effect of methylglyoxal had been known for a long time. The present work shows that this anticancer effect of methylglyoxal is significantly augmented in presence of creatine. On creatine supplementation the effect of methylglyoxal plus ascorbic acid was further augmented and there was no visible sign of tumor. Moreover, creatine and CK, which were very low in sarcoma tissue, were significantly elevated with the concomitant regression of tumor.

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